人类阴道微生物组(vaginal microbiome,VMB)在维持人体健康和微生态平衡方面起着至关重要的作用,与其他器官的微生物组相比,VMB表现出低多样性。宫颈癌(cervical cancer,CC)是女性常见的恶性肿瘤,已证实与高危型人乳头瘤病毒(human papilloma virus,HPV)的持续感染高度相关。阴道微生物与HPV感染和宫颈病变存在相关性,一方面乳杆菌可降低宫颈细胞的通透性,减少炎症反应,抑制宫颈癌细胞的生长,而非乳杆菌主导的高多样性阴道菌群可表达与宫颈细胞黏附及毒性相关的基因,损伤宫颈及上皮细胞,引起HPV感染和高级别宫颈上皮内瘤变;另一方面,HPV 相关E7癌蛋白可通过NF-β-κB和Wnt/β-catenin信号通路减少防御肽的分泌,从而抑制乳杆菌生长,导致阴道pH值升高和阴道致病菌的生长,引起VMB的结构变化。本文主要讨论VMB、HPV持续感染和宫颈病变之间的关系及病因,旨在寻找VMB相关疾病的新靶点。
The human vaginal microbiota (VMB), which plays a vital role in maintaining health and homeostasis, exhibits low diversity compared to the microbiomes of other organs. Cervical cancer (CC) is a common malignancy in women and has been shown to be highly associated with persistent infection with high-risk human papillomavirus (HPV). VMB is associated with human papillomavirus infection and cervical lesions, and may play a positive role in the progression of HPV infection and cervical intraepithelial neoplasia (CIN). On the one hand, lactobacillus can reduce the permeability of cervical cells, and reduce inflammatory response, inhibit the growth of cervical cancer cells, but the bacterias enhancing the diversity of VMB can express virulence and attachment genes, which cause damage to cervix and epithelial cells, causing HPV infection and high-grade disease states; On the other hand, HPV-associated E7 oncoprotein can reduce the secretion of defense peptides which are conducive to the growth of lactobacillus through NF-β-κB and Wnt/β-catenin signaling pathways, resulting in an increase in vaginal pH, which further facilitates the growth of vaginal pathogenic bacteria, and ultimately leads to structural changes of VMB. This review focuses on the relationship between the vaginal microbiome, persistent HPV infection and cervical dysplasia and the factors that mediate these relationships, which will help to find new targets for VMB-related diseases.